Limits...
The transcription factor lymphoid enhancer factor 1 controls invariant natural killer T cell expansion and Th2-type effector differentiation.

Carr T, Krishnamoorthy V, Yu S, Xue HH, Kee BL, Verykokakis M - J. Exp. Med. (2015)

Bottom Line: These cells acquire multiple effector fates during their thymic development that parallel those of CD4(+) T helper cells.LEF1 also directly augments expression of the effector fate-specifying transcription factor GATA3, thus promoting the development of Th2-like effector iNKT cells that produce IL-4, including those that also produce interferon-γ.Our data reveal LEF1 as a central regulator of iNKT cell number and Th2-type effector differentiation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.

Show MeSH

Related in: MedlinePlus

TCF1 expression was not affected by deletion of Lef1 in iNKT cells. (A) Expression of LEF1 and TCF1 in total WT FVB/NJ iNKT cells, as determined by flow cytometry. (B) TCF1 expression in the indicated iNKT stages (left) or iNKT subsets (right) from WT FVB/NJ thymocytes was determined by flow cytometry and is shown as histograms. Solid gray or control represents anti-TCF1 staining in TCF1-deficient iNKT cells and serves as a negative control. (C and D) TCF1 expression in CD4+ and DN (C) or ST1, ST2, and ST3 (D) thymic iNKT cells from control and Lef1Δ/Δ mice was determined by flow cytometry. Data are representative of four independent experiments.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4419352&req=5

fig7: TCF1 expression was not affected by deletion of Lef1 in iNKT cells. (A) Expression of LEF1 and TCF1 in total WT FVB/NJ iNKT cells, as determined by flow cytometry. (B) TCF1 expression in the indicated iNKT stages (left) or iNKT subsets (right) from WT FVB/NJ thymocytes was determined by flow cytometry and is shown as histograms. Solid gray or control represents anti-TCF1 staining in TCF1-deficient iNKT cells and serves as a negative control. (C and D) TCF1 expression in CD4+ and DN (C) or ST1, ST2, and ST3 (D) thymic iNKT cells from control and Lef1Δ/Δ mice was determined by flow cytometry. Data are representative of four independent experiments.

Mentions: We questioned whether LEF1 deficiency was affecting the expression of TCF1 in iNKT cells because TCF1 is essential for CD4+ Th2 cell differentiation and ILC2 development and is generally redundant with or dominant to LEF1. TCF1 was expressed in all iNKT cells, and LEF1 expression was directly correlated with TCF1 in a subset of these cells (Fig. 7 A). Like LEF1, TCF1 was expressed most highly in ST1 and ST2 iNKT cells (Fig. 7 B); however, TCF1 was expressed in both CD4+ and DN iNKT cells and in ST3 iNKT cells (Fig. 7, B and C). Consistent with this expression pattern, TCF1 was expressed in iNKT2 and iNKT17 cells at levels comparable with cCD4+ T cells and at lower levels in iNKT1 cells (Fig. 7 B). Importantly, TCF1 was expressed equally well in control and Lef1Δ/Δ ST1 and ST2 iNKT cells, indicating that the alterations in iNKT cell development caused by LEF1 deficiency were not a consequence of a loss of TCF1 (Fig. 7 D). TCF1 expression was increased slightly in Lef1Δ/Δ ST3 iNKT cells, suggesting that there may be a selection for TCF1 in these cells or their progenitors when LEF1 is absent (Fig. 7 D). Therefore, our data revealed critical functions for LEF1 in iNKT cell expansion and the development of iNKT2 cells that were not compensated for by TCF1 despite TCF1 expression in all iNKT cells.


The transcription factor lymphoid enhancer factor 1 controls invariant natural killer T cell expansion and Th2-type effector differentiation.

Carr T, Krishnamoorthy V, Yu S, Xue HH, Kee BL, Verykokakis M - J. Exp. Med. (2015)

TCF1 expression was not affected by deletion of Lef1 in iNKT cells. (A) Expression of LEF1 and TCF1 in total WT FVB/NJ iNKT cells, as determined by flow cytometry. (B) TCF1 expression in the indicated iNKT stages (left) or iNKT subsets (right) from WT FVB/NJ thymocytes was determined by flow cytometry and is shown as histograms. Solid gray or control represents anti-TCF1 staining in TCF1-deficient iNKT cells and serves as a negative control. (C and D) TCF1 expression in CD4+ and DN (C) or ST1, ST2, and ST3 (D) thymic iNKT cells from control and Lef1Δ/Δ mice was determined by flow cytometry. Data are representative of four independent experiments.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4419352&req=5

fig7: TCF1 expression was not affected by deletion of Lef1 in iNKT cells. (A) Expression of LEF1 and TCF1 in total WT FVB/NJ iNKT cells, as determined by flow cytometry. (B) TCF1 expression in the indicated iNKT stages (left) or iNKT subsets (right) from WT FVB/NJ thymocytes was determined by flow cytometry and is shown as histograms. Solid gray or control represents anti-TCF1 staining in TCF1-deficient iNKT cells and serves as a negative control. (C and D) TCF1 expression in CD4+ and DN (C) or ST1, ST2, and ST3 (D) thymic iNKT cells from control and Lef1Δ/Δ mice was determined by flow cytometry. Data are representative of four independent experiments.
Mentions: We questioned whether LEF1 deficiency was affecting the expression of TCF1 in iNKT cells because TCF1 is essential for CD4+ Th2 cell differentiation and ILC2 development and is generally redundant with or dominant to LEF1. TCF1 was expressed in all iNKT cells, and LEF1 expression was directly correlated with TCF1 in a subset of these cells (Fig. 7 A). Like LEF1, TCF1 was expressed most highly in ST1 and ST2 iNKT cells (Fig. 7 B); however, TCF1 was expressed in both CD4+ and DN iNKT cells and in ST3 iNKT cells (Fig. 7, B and C). Consistent with this expression pattern, TCF1 was expressed in iNKT2 and iNKT17 cells at levels comparable with cCD4+ T cells and at lower levels in iNKT1 cells (Fig. 7 B). Importantly, TCF1 was expressed equally well in control and Lef1Δ/Δ ST1 and ST2 iNKT cells, indicating that the alterations in iNKT cell development caused by LEF1 deficiency were not a consequence of a loss of TCF1 (Fig. 7 D). TCF1 expression was increased slightly in Lef1Δ/Δ ST3 iNKT cells, suggesting that there may be a selection for TCF1 in these cells or their progenitors when LEF1 is absent (Fig. 7 D). Therefore, our data revealed critical functions for LEF1 in iNKT cell expansion and the development of iNKT2 cells that were not compensated for by TCF1 despite TCF1 expression in all iNKT cells.

Bottom Line: These cells acquire multiple effector fates during their thymic development that parallel those of CD4(+) T helper cells.LEF1 also directly augments expression of the effector fate-specifying transcription factor GATA3, thus promoting the development of Th2-like effector iNKT cells that produce IL-4, including those that also produce interferon-γ.Our data reveal LEF1 as a central regulator of iNKT cell number and Th2-type effector differentiation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.

Show MeSH
Related in: MedlinePlus